This is an application requesting support to continue a Training Program initiated in 1994 devoted to the rigorous training of: (1) highly motivated physicians who have completed their clinical training in the disciplines of Rheumatology or Orthopedics; (2) physicians who have chosen to obtain a Ph.D. degree during their training in Orthopedics; (3) recently graduated Ph.D.'s committed to conduct research applicable to Rheumatology or Orthopedic diseases; and (4) Internal Medicine Residents entering the newly approved Internal Medicine-Subspecialty Research pathway. The program provides closely supervised intensive laboratory experience emphasizing the application of state of the art methods of Molecular Biology, Genetics, Cell Biology and Biochemistry towards the investigation of the etiology and pathogenesis of diseases affecting the connective tissues and the musculoskeletal system. The major strengths of this Training Program are: (1) the comprehensive and multi-disciplinary approach to the study of disorders of great public health and socioeconomic importance which affect a large segment of the population; (2) the cadre of highly productive and accomplished investigators that have been selected from the numerous members recruited in the recent past to Thomas Jefferson University; (3) the diverse nature of the expertise and research interests of the faculty and their application of the most advanced molecular biological approaches to the study of various rheumatic and musculoskeletal diseases; and (4) the long-term commitment of the faculty to the training of Physician Scientists and Ph.D.'s. The program we established represents a consolidation of various training activities previously ongoing at our institution into a unified program which is highly focused on the study of the etiology and pathogenesis of rheumatic and musculoskeletal diseases. The training opportunities offered have the unifying goal of preparing the trainees in the application of the most advanced methods of Molecular Biology, Genetics, Cell Biology and Biochemistry to the study of a broad spectrum of diseases affecting the musculoskeletal system. The training activities consist of directly supervised laboratory research supplemented by formal course work, attendance to a large number of scheduled lectures and seminars, attendance to and presentation of journal clubs, and presentation of research results at institutional and national meetings. At the completion of the program, the trainees will be extremely well prepared to obtain academic appointments and to pursue careers as Physician- Scientists or as Ph.D.'s capable of establishing independent research programs in areas relevant to Rheumatology and Orthopedics.